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Leveraging the Tools and Techniques of Precision Medicine to Better Understand the Biological Underpinnings of Psychiatric Disorders and Psychotropic Treatment Effects

  • Author(s): Seaman, Lauren C
  • Advisor(s): Nurmi, Erika L
  • et al.
Abstract

The dawn of a new era of medicine has begun as clinicians and researchers shift their focus to more individual-centric diagnostic, treatment, and disease management strategies. Precision medicine is a multidisciplinary approach to human health care that takes into account a person’s genetic makeup, behaviors, and environmental factors when evaluating pathophysiology, tailoring treatments, and designing novel therapeutic moieties. In this dissertation I break down the critical subfields of this discipline to explain and apply the emerging tools and techniques we now have at our disposal to better understand the underlying biology of complex human psychiatric disorders.

We begin with pharmacokinetics and pharmacodynamics, two branches of precision medicine that are involved directly with the temporal dynamics of pharmaceutical therapies and aid in disentanglement of how the body processes drugs versus how the drugs affect our bodies. I discuss detailed research across three separate drugs; risperidone, methamphetamine, and nicotine, integrating quantitative metabolic studies, genetic assessment, neuroimaging, and receptor analysis to clearly define inter-patient variability in risk and response.

Following this is work I accomplished in the realm of gene and environment interactions in young children experiencing anxiety disorders, which over time, led to what I hold as my largest contribution to the personalized medicine field; microbiome and host interactions. I am attempting to unlock a more direct, biological mechanism to something known as antipsychotic-induced weight gain (AIWG) through the examination of bile acids and the gut microbiome and their crosstalk and interplay with host physiology. Results are abundant throughout this document and each study presented here within brings a unique piece of the precision medicine puzzle to the table.

Pharmacokinetics, pharmacodynamics, genomic technology, gene-environment interactions, and the host-microbiome axis are the salient concepts in my toolbox of personalized medicine techniques that I believe can be leveraged in a variety of combinations to accomplish large goals in the medical and biotechnology fields. Whether it be through careful patient assessment with companion diagnostics, proper medication selection based on risk vs. reward value in harmony with an individual’s personal makeup, perseverance of high level disease progression and treatment monitoring, or even one day tailoring drug discovery to the highly specific receptors and biological pathways involved in these grievous diseases, it is clear precision medicine will pave the way for a better life for many people in the future.

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